The goal of this project is to comprehensively establish the pathway of T cell activation. We intend to define and order the external signal signals and intracellular messengers responsible for 1 degree and 2 degree T cell stimulation and link those events with sequence of gene activation that governs the activation process. In short, we will identify and sequence the physiologic extracellular stimuli causing T cell activation, identify the intracellular messengers activated by these stimuli, linking the stimuli and intracellular messengers to gene activation, and identify the sequence of T cell activation antigen associated gene activation. The specific aims are: 1. To identify and sequence the physiologic extracellular stimuli yielding T cell activation. 2. To identify the the intracellular messengers activated by each of these extracellular stimuli. 3. To identify the mechanisms by which these stimuli and intracellular messengers cause gene activation. 4. To identify the sequence of T cell activation associated gene activation. These data should provide a comprehensive framework by which T cell immunobiology and immunopharmacology can be examined in health and disease.